Abstract
The knowledge regarding the role of caveolin-1 (Cav-1) protein on endothelium adhesion of cancer cells is unclear. The present study revealed that Cav-1 plays a negative regulatory role on cancer-endothelium interaction. Endogenous Cav-1 was shown to down-regulate during cell detachment and the level of such a protein was conversely associated with tumor-endothelial adhesion. Furthermore, the ectopic overexpression of Cav-1 attenuated the ability of the cancer cells to adhere to endothelium while shRNA-mediated Cav-1 knock-down exhibited the opposite effect. We found that cell detachment increased cellular hydrogen peroxide and hydroxyl radical generation and such reactive oxygen species (ROS) were responsible for the increasing interaction between cancer cells and endothelial cells through vascular endothelial cell adhesion molecule-1 (VCAM-1). Importantly, Cav-1 was shown to suppress hydrogen peroxide and hydroxyl radical formation by sustaining the level of activated Akt which was critical for the role of Cav-1 in attenuating the cell adhesion. Together, the present study revealed the novel role of Cav-1 and underlying mechanism on tumor adhesion which explain and highlight an important role of Cav-1 on lung cancer cell metastasis.
Highlights
Roles of caveolin-1 (Cav-1) in regulation of cancer progression and metastasis in various types of cancer have been revealed [1,2,3,4] and such a protein perhaps received the most attention in cancer-related research
MO); Rabbit caveolin-1 antibody and peroxidase-conjugated secondary antibody from Abcam (Cambridge, MA); Hydrophenyl fluorescein (HPF), LY294002, Amplex Red, Lipofectamine 2000 were from Invitrogen (Carlsbad, CA); Antibody for b-actin from Santa Cruz Biotechnology (Santa Cruz, CA); Antibody for pan-Akt, p473-Akt, PTEN, EGFR, Phospho-PTEN (Ser380/Thr382/383) were from Cell Signaling Technology, Inc. (Danvers, MA); Endothelial cell growth supplement was from Millipore Corporation (Billerica, MA)
Together with the above finding indicating that Cav-1 attenuated hydrogen peroxide and hydroxyl radical formations during cell detachment, we investigated whether hydrogen peroxide and hydroxyl radical play a role in regulating cancer cell adhesion
Summary
Roles of caveolin-1 (Cav-1) in regulation of cancer progression and metastasis in various types of cancer have been revealed [1,2,3,4] and such a protein perhaps received the most attention in cancer-related research. Hydrogen peroxide was shown to increase the cellular level of Cav-1 by inhibiting its degradation [6]. While in the adherent cells, hydroxyl radical was shown to be a key player in up-regulating Cav-1 expression and increased cell migration [11]. These findings highlighted the regulatory role of ROS on Cav-1 expression and their accompany roles on cancer metastasis
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